Measurement of the composition of a gas mixture is especially important in the airway of an individual who is connected to an auxilliary breathing apparatus. Examples include ventilators which assist respiration in the intensive care unit and coronary care unit in hospitals, and anesthesia machines in hospital operating rooms ("ORs"). These patients are often monitored closely for their vital signs, including respiratory gas exchange.
In the operating room, the anesthesiologist supports the patient's respiration and also controls the patient's depth of anesthesia using special gaseous agents. A patient airway will contain the normal respiratory gases, such as oxygen (O.sub.2), carbon dioxide (CO.sub.2), and water vapor (H.sub.2 O), or a mixture of nitrous oxide (N.sub.2 O) and one or more halogenated anesthetic agents ("HA", usually halothane, enflurane, isoflurane, desflurane or sevoflurane). Occasionally, nitrogen (N.sub.2) from room air infiltrates the system. Various metabolic products and special gases, for example, to measure pulmonary function, may also be present. Also, interferences from extraneously introduced gases such as ethanol and isopropanol may be present. Because severe injury can result from use of an improper gas mixture, anesthesiologists prefer to measure the composition of the patient breathing mixture. Every component of the mixture is important. Measurement of oxygen concentration helps prevent hypoxia. Presence of the CO.sub.2 waveform indicates healthy gas exchange. Measurement of the type and concentration of the various anesthetic agents helps control and adjust the proper depth of anesthesia. The presence of other gases can indicate leaks and possible system malfunctions.
Several Anesthesia Monitors ("AMs") exist today that perform this function. Four different technologies compete for most of the market today.
(1) Infrared Absorption plus Oxygen. One class of AMs uses infrared absorption to measure the halogenated anesthetics, CO.sub.2, and N.sub.2 O. While this technique is widely used, it has the disadvantages that it is difficult to distinguish the HAs from each other, because they have similar IR spectra that must be measured in the region .lambda.=3-4 .mu.m. Identification of the individual agents requires measurement in the far infrared region, .lambda.&gt;10 .mu.m, which is more difficult. A separate measurement, using a paramagnetic or polarographic sensor, is needed to measure O.sub.2, which has no infrared ("IR ") spectrum. Also, separate cells are needed to measure the HAs and the CO.sub.2 +N.sub.2 O concentrations. In addition, these devices have no means to detect other gases which may be present. Such devices may introduce error in the measurements, and the devices cannot be adapted easily to measure new agents.
(2) Mass Spectrometry. Mass spectrometers ("MS") can provide extremely accurate measurements of gas concentrations. Historically, MS devices are expensive and complicated instruments that require frequent calibration and maintenance. These devices require use of a delicate vacuum system and ion source. Typically, many operating rooms share a single MS. This reduces the response time between measurements, and requires relatively long sampling lines, which can distort the gas samples. In addition, the mass spectra of the various OR gases are not unique. Nitrous oxide and carbon dioxide have the same mass number, and isoflurane and enflurane are isomers. Therefore, one must observe fragmentation of these molecules in the system and employ special algorithms to distinguish the molecules. The systems must also be protected from some other gases, including helium and water vapor. Shared systems cannot provide continuous, breath-to-breath analysis of airway concentrations, which is desirable. At least one manufacturer has introduced a small, stand-alone MS, offering each OR suite a dedicated measuring device. Although this device eliminates the problem of multiplexing measurements for different users, and has a more convenient design, the device still requires protection from contaminants, and can only be configured to measure a few specific gases at a time. The problems of high cost and distinguishing between isomers and between identical mass spectra remain.
(3) Photo-acoustic Spectroscopy. These devices also utilize the properties of infrared absorption to characterize gas mixtures. A precision microphone detects pressure waves which are produced when the gas sample absorbs IR energy. The sound level indicates the concentration. Like the IR systems described above, these devices need a separate system to measure oxygen concentration, and the technique cannot easily distinguish different HAs from each other.
(4) Raman Spectroscopy. Scattering of light by the Raman effect has received much attention from scientists since its original exposition by C. V. Raman in 1928. Simply stated, when monochromatic light illuminates a vibrating molecule, light scatters in a process which decreases or increases the frequency of the scattered light by exactly the vibrational frequency of the molecule. The shift in frequency of radiation is characteristic of the scattering medium, and is independent of the frequency of the illuminating radiation. Thus, measurement of the Raman-scattered light can be used to infer the properties of the medium, such as the chemical composition and concentration. For measurements of OR and airway gases, this technique has the advantage that each OR gas, including oxygen and any poly-atomic molecule, has a unique Raman spectrum. Additionally, the Raman spectrum for a gas is usually contained in a relatively narrow wavelength band, which simplifies detection. Thus, Raman spectroscopy offers the promise of simultaneous measurement of all airway gases with a single measurement and less complex technology.
In Raman scattering, a small fraction of collisions of photons with an atom or molecule are inelastic, with a photon either giving up a small portion of its initial energy E.sub.0 to the collision partner and scattering as a photon of reduced energy E &lt;E.sub.0 (Stokes waves) or the collision partner giving up a small portion of its initial energy so that the photon scatters with increased energy E&gt;E.sub.0 (anti-Stokes waves). In Rayleigh scattering of a photon with an atom or molecule, by contrast, the energy of the scattered photon is equal to the initial energy of the photon. This does not include light that is absorbed and re-emitted by processes such as phosphorescence or fluorescence. In a typical scattering situation, the ratio of intensity of Rayleigh to initial light intensity for gases might be about 10.sup.-9 and the ratio of intensity of Raman scattered light to initial light intensity might be about 10.sup.-12. The change in wavelength for a Raman scattered photon of initial wavelength .lambda..sub.0 =c/f.sub.0 and scattered light wavelength .lambda..sub.R =c/f.sub.R is given by EQU .DELTA..lambda.=.lambda..sub.R -.lambda..sub.0 =(c/f.sub.R)-(c/f.sub.0),(1)
where .DELTA..lambda.&gt;0(.DELTA..lambda.&lt;0) corresponds to appearance of Stokes waves (anti-Stokes waves). Substantially all scattered light at moderate initial energies arises from Rayleigh scattering or Raman scattering. For molecules of moderate or higher symmetry, not all modes of molecular vibration result in Raman lines. Some of the modes of molecular vibration produce infrared absorption lines but not Raman scattering lines, some modes produce Raman lines but not infrared lines, some modes produce both Raman and infrared lines, and some vibration modes produce neither Raman nor infrared lines.
The Raman scattering cross-sections are extremely small, and the intensity of the scattered light is very weak, as noted above, especially in gases where the molecular number density is also relatively small (compared to liquids and solids), and are therefore difficult to measure with accuracy. The differential intensity of the Raman-scattered light scattered into a differential solid angle d.OMEGA. along a differential path length dz in a single component gas is given by the formula EQU dP.sub.Raman =P.sub.o n.sub.o (d.sigma./d.OMEGA.)d.OMEGA.dz,(2)
where P.sub.o is the intensity of the incident light, n.sub.o is the number density of the scattering molecules, and (d.sigma./d.OMEGA.) is the differential scattering cross-section in a given direction. The direction of the scattering is also dependent on the polarization of the incident light. If the gas contains more than one component and the components do not interact appreciably with one another, the intensity of each Raman line of a gas component is proportional to the concentration of that component so that Equation (2) above can be used with a small modification to take account of the presence of the other components.
For a given intensity of the incident radiation and sample concentration, one can maximize the magnitude of the measured Raman signal only by increasing the solid angle of the light-collecting optics, or by increasing the observation path length (i.e., using a larger scattering volume), because the molecular properties of the sample are not variable.
In a conventional system for observing Raman-scattered light, a laser beam is brought to a focus in the medium of interest, creating a minute region of relatively intense electrical field, which excites the Raman effect. The light scattered from this region is collected by an optical system, typically a simple lens which images the scattering region onto a suitable optical filter and detector. The difficulty of improving this simple design is evident from the observation that the etendue (defined as the product of the collection area and collection solid angle) is conserved in any ideal optical system. Thus, increasing the solid angle of light collection (lower f number optics) decreases the observable area (and thus the path length). Each experimental system must optimize these parameters against its own constraints. Some Raman systems further improve signal intensity by providing multiple passes of the incident light beam through the observation volume, effectively increasing the path length, or by placing the observation volume inside an optically resonant cavity, effectively increasing the incident intensity P.sub.o.
Analysis of Raman scattered light is especially useful where the Raman spectrum of each of the components present in a sample is a relatively simple line pattern and the Raman lines of the different components do not coincide with or lie close to one another. A complete range of vibrational frequencies can be covered with one monitoring instrument, and the sample container can be glass or many other relatively transparent materials. Water may be present; the Raman spectrum of water is weak and diffuse in the band 200-3300 cm.sup.-1, but the spectrum has a strong, broad peak centered at 3652 cm.sup.-1. The approximately linear relationship between component concentration and Raman-scattered light intensity makes the calculation of concentration straightforward. Integration across a portion of the Raman spectrum to determine the intensity of specified lines is also straightforward. However, the sample should be non-fluorescent, and the sample to be analyzed should be relatively transparent, with little or no absorption at the wavelengths of interest, and should be free of particulates. It is often difficult to apply Raman scattering to very low concentrations of the sample, because of the weak intensity of the individual Raman lines.
Raman systems that measure the composition in patient airways must measure multiple spectral lines in order to distinguish all the component gases. Several earlier patents describe techniques for measuring multiple gases.
Albrecht, in German Pat. DE 2723939C2, describes a system of six detectors mounted in an equatorial plane around a region of focus. The focal region has a confocal cavity where the exciting laser beam makes multiple passes through the sample. This system requires six different detection channels, each with associated collection optics, laser line rejection and Raman line filters, and separate detector. The configuration is limited to six channels and uses an unpolarized laser beam. More channels would be needed to measure all the OR gases of interest. In addition, the confocal cavity and each of the collection optics requires delicate adjustment to assure proper imaging of the focal region onto the detectors.
In U.S. Pat. No. 3,704,951, Chupp discloses use of a multi-pass gas cell for increasing the intensity level of light that is Raman scattered from a gas sample contained in the cell. Raman scattered light exits from the cell through a large side window in the cell.
Leonard, in U.S. Pat. No. 3,723,007, discloses a gas cell with a transparent side window for Raman scattering analysis and notes that two or more simple molecular gases may have distinct Raman shift spectra.
A spectrophotometer that compares light Ramnan scattered from a known gas sample with light Raman scattered from an unknown gas sample is disclosed by Tans et al in U.S. Pat. No. 4,630,923. Raman scattered light from the known and unknown gas samples is alternatingly received by a detector to determine the concentration ratios of two gases present in the unknown gas sample.
A gas monitoring system, disclosed by Benner et al in U.S. Pat. No. 4,648,714, collects light from a single focal region, illuminated by a properly oriented, polarized laser beam. A single set of collection optics images the scattered light onto a single detector. An additional mirror, placed opposite the collection optics, reflects Raman-scattered light back into the focal region and into the collection optics, further enhancing the signal. The sample cell can be inside the resonant cavity of the exciting laser to increase the signal still more. The system employs a rotating filter wheel that passes different Raman line filters in front of the detector so that different Raman lines are measured sequentially. While this system can measure a larger number of Raman spectral lines (by adding more filters), the samples are not acquired simultaneously from the same gas sample. This reduces the ability of the system to respond rapidly, as is desired for breath-by-breath analysis of the airway composition.
In U.S. Pat. No. 4,676,639, Van Wagenen discloses use of a gas cell for Raman scattering analysis with transparent end and side windows. The side windows may be coated with a narrow band anti-reflection coating, for passage of the Raman scattered light for detection outside the gas cell.
Van Wagenen et al describe another system in U.S. Pat. No. 4,784,486, which uses multiple detection units, each including collection optics (lens and back reflector), laser line rejection and Raman line filters, and a detector. Each detection unit collects Raman-scattered light simultaneously from separate focal regions. The system is similar to the system of Bennet, but employs a completely separate detection unit for each Raman line, rather than inserting different filters serially. This design has the advantage that all the channels can acquire measurements simultaneously. However, the measurements are generated from different sample volumes and, thus, from different gas molecules. The sample gas must flow from location to location, and the flow rate must be such that all units see a mixture of substantially similar composition. Thus, for a given flow rate and size of sample cell, the practical number of detector units is limited by the desired time response of each system. This creates limitations because it is desirable to sample as small a volume as possible from the patient airway. An increase in the number of detection units increases the expense of the unit proportionally. Each unit also requires separate alignment and adjustment, which increases the complexity and cost of the system.
Many of the systems discussed above employ a combination of individual narrow-band filters. Each individual filter examines only a single spectral line or a small spectral region. This requires that a system use at least one filter for every molecule spectral peak of interest. Allowing for the expense of multiple channels and filters, these systems are suited to the measurement of gas mixtures, where the Raman spectrum of each gas consists of a single peak or a few well-separated peaks, and where these spectral peaks are unique for each gas in the mixture, with no overlapping spectral lines. In this case, each filter can measure each gas separately and completely. Overlapping spectral lines can be ignored if the gas of interest has another unique peak. This is true for the gases N.sub.2, O.sub.2, CO.sub.2, and N.sub.2 O. The principal spectral lines of these gases are listed below as frequency shifts from the frequency of the illuminating source, such as a laser beam. Note that CO.sub.2 and N.sub.2 O have an overlapping line at 1285 cm.sup.-1.
N.sub.2, nitrogen: 2331 cm.sup.-1 PA1 O.sub.2, oxygen: 1555 cm.sup.-1 PA1 CO.sub.2, carbon dioxide: 1285 and 1388 cm.sup.-1 PA1 N.sub.2 O, nitrous oxide: 1285 and 2224 cm.sup.-1
The limitations of these types of systems, which employ separate filters, arise when the Raman spectra of one molecule of interest becomes complicated, when it covers a larger spectral band or has many, scattered peaks, such as the halogenated anesthetics. These spectra are best characterized by their entire spectrum, not by single lines. The Raman spectra from the HAs have considerable spectral overlap with each other, and the broadband emission can contribute error to the signals of the respiratory gases and N.sub.2 O. A representative mixture of the respiratory and anesthetic gases produces a complicated signal, with emissions and spectral lines across the entire spectrum, a mixture of all the individual spectra. Measurement of single spectral lines therefore gathers less signal and less information than a technique that gathers the entire spectral signature of the mixture or of a single component. Single filter systems use only small amounts of the total signal available, because such systems measure only part of the Raman emissions. For the HAs, measurement of a single line neglects most of the total signal. Single filter systems also neglect significant information about the Raman spectra. It is much easier to distinguish each HA from examination of its entire spectrum than from a single, possibly weak, line.
A further limitation of the single filter system is that new or additional gases cannot be measured without the addition of new detection units with new filters. New gases which have substantial spectral overlap with existing gases may be very difficult to measure, even with additional filters.
Also, if a Raman spectrum has closely spaced lines that must be distinguished from each other, the spectral bandwidth of the individual filters must be sufficiently narrow to differentiate nearby lines, or obscure undesired lines. This places a constraint on the spectral bandwidth of the laser source, which must be at least as narrow as the Raman line filters, and the laser must not drift in wavelength. This constraint also reduces the detected power. Further, filters can drift as they age. If a filter has a bandwidth of 1 nm, and the laser drifts in wavelength from 800 nm to 803 nm, the Raman line of interest moves out of the band of the filter and is not measurable. For these reasons, existing filter-based Raman systems often use gas lasers, such as argon-ion, which has narrow, constant lines and requires high input power. Solid-state lasers have wider line widths (&gt;1 nm), and often require special wavelength stabilization. Semiconductor lasers presently require low input power and produce wider linewidths.
What is needed is a gas monitoring system that (1) allows simultaneous determination of the concentration of components in a multiple component gas; (2) is very efficient and uses as much of the total signal available as possible for examination of the spectrum; (3) allows interrogation of a broad spectrum in a single measurement of a small single sample; (4) allows distinctions to be made relatively easily between gas components that may be present; (5) allows considerable freedom in the choice of sample container and sample concentration; (6) allows the system to monitor and identify different compounds with minimal system modifications; and (7) allows use of low power light sources and of relatively low cost detectors.